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Abstract

M. Tolnay and S. Frank

Department of Neuropathology, Institute of Pathology, University Hospital Basel, Basel, Switzerland
Frontotemporal lobar degeneration (FTLD) is a common form of dementia that usually afflicts patients in their mid-life. Clinically, patients with FTLD present with changes in behavior and/or language dysfunction. According to their underlying neuropathological substrate, these neurodegenerative conditions can now be classified into two main groups: those with t pathology (tauopathies), and those without t pathology. In the majority of nontauopathy disorders the recently identified TAR DNA-binding protein-43 (TDP-43) is found as the major inclusion protein (TDP-43 proteinopathies), and TDP-43 is also present in motor neuron inclusions of amyotrophic lateral sclerosis. Presently, mutations in 4 genes (MAPT, PGRN, VCP, CHMP2B) are known to cause diverse types of FTLD pathology. Here, we summarize the recent neuropathological and genetic advances in FTLD research.Correspondence to:
Prof. M. Tolnay; Institute of Pathology, Department of Neuropathology, University Hospital Basel, Schönbeinstraße 40, 4031 Basel, Switzerland
Email: mtolnay@uhbs.ch

Abstract

F. Hanisch, C.R. Müller, D. Grimm, L. Xue, K. Traufeller, A. Merkenschlager, S. Zierz and M. Deschauer

¹Klinik und Poliklinik für Neurologie, Universität Halle-Wittenberg,
²Institut für Humangenetik der Universität Würzburg and
³Klinik und Poliklinik für Kinder und Jugendliche, Universität Leipzig, Germany
Objective: Calpain-3 deficiency is the most common cause of autosomal-recessive limb girdle muscular dystrophy (LGMD2). The c.550delA mutation in the CAPN3 gene was frequently identified in LGMD2A patients from Eastern Europe and is considered a Slavic founder mutation. Methods: We screened for the c.550delA mutation in unrelated German patients with LGMD2 (n = 98) and in patients with asymptomatic or minimally symptomatic (myalgia or fatigue) hyperCKemia of unknown origin (n = 102). Results of Western blot analysis were available in 75 patients with LGMD2 and 65 patients with hyperCKemia. In samples that were heterozygous for the c.550delA mutation, the whole CAPN3 gene was analyzed by sequencing in order to detect the second mutation. Results: The c.550delA mutation was found in 8.1% of LGMD2 (n = 1 homozygous, n = 7 heterozygous) and 1.9% of hyperCKemia patients (n = 2 heterozygous). In 8 of the 9 hetrozygous patients, a second CAPN3 mutation was identified by direct sequencing. Two mutations (Val509Phe and Gln565Stop) have not been reported before. Absent or deficient calpain-3 protein in Western blot analysis was found in 22.5% of the LGMD2 patients and 11% of the patients with hyperCKemia. Western blot results were available in 9 out of the 10 patients with genetically confirmed LGMD2A and were clearly abnormal in 6 patients, suspicious in 2 and entirely normal in 1. Two LGMD2 patients with the c.550delA mutation and onset within the first 2 decades had joint contractures. Muscle biopsy revealed inflammatory changes in three patients. Conclusion: The CAPN3 gene mutation c.550delA is rather frequently observed in German patients with LGMD2, but also occasionally in cases with isolated hyperCKemia.Correspondence to:
Dr. med. F. Hanisch; Klinik und Poliklinik für Neurologie, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Straße 40, 06097 Halle/Saale
Email: frank.hanisch@medizin.uni-halle.de

Abstract

S. Schoeler, S. Hertel, M.F. Haroon, K. Winkler-Stuck, C. Mawrin and E. Kirches

¹Institute of Neuropathology, ²Neurological Hospital and ³Institute of Medical Neurobiology of the Otto von Guericke University, Magdeburg, Germany ⁴Instiute of Neuropathology of the Friedrich Schiller University, Jena, Germany
The pathogenesis of the selective loss of dopaminergic neurons in idiopathic Parkinson’s disease (PD) has not been understood up to now. Respiratory chain dysfunction and accumulation of mitochondrial DNA deletions to biochemically relevant levels have been observed in the dopaminergic neurons. However, respiratory chain defects have also been reported in other tissues, pointing to a generalized component of oxidative stress in PD. Recently, somatic point mutations in a narrow region of the complex I polypeptide ND5 (codons 120 – 150) were suggested to separate PD patients from age-matched controls, using frontal cortex homogenates. Objective: The present study intended to analyze whether those recently described ND5 mutations may also generally occur in skeletal muscle tissue of PD patients, in which complex I dysfunction had been measured earlier with biochemical approaches. Material: Skeletal muscle biopsy samples of 5 PD individuals with a previously characterized biochemical complex I defect and of 5 age-matched controls were used. Method: DNA was extracted from the muscle samples. The relevant ND5 region was PCR-cloned using a high fidelity Pfu polymerase and a low number of PCR cycles (15). A mean number of 96 clones were randomly selected from the ampicillin plates and sequenced by the dye terminator method to allow the detection of low abundance mutations with a sensitivity around 1%. Results: Mutations between codons 120 and 150 were only slightly more frequent in PD versus controls (60 versus 40% of samples affected), while this ratio had been 100 versus 12.5% in frontal cortex. Conclusions: In contrast to results reported for PD frontal cortex, low-level ND5 mutations between codons 120 and 150 do not accumulate severely in biochemically affected skeletal muscle samples of PD patients.Correspondence to:
Dr. E. Kirches; Institut für Neuropathologie, Otto-von-Guericke-Universität, Leipziger Straße 44, 39120 Magdeburg, Germany
Email: Elmar.kirches@medizin.uni-magdeburg.de

Abstract

K. Ishizawa, S. Terao, K. Kobayashi, K. Yoshida and T. Hirose

¹Department of Pathology, Saitama Medical University,
²Department of Neurosurgery, Saitama Hospital and
³Department of Neurosurgery, Keio University Hospital, Saitama, Japan
A neuroepithelial tumor showing combined histological features of dysembryoplastic neuroepithelial tumor (DNT) and pleomorphic xanthoastrocytoma (PXA) is described. The patient was a 60-year-old male with a long-standing temporal lobe tumor and seizures. After a long, dormant period, the tumor, which had been localized in the left uncus, re-grew rapidly and extended into the subarachnoidal space and brain stem. The post-operative specimens disclosed two distinct components: an intra-cortical, cystic lesion containing mucinous materials and an extra-cortical, nodular lesion involving the leptomeninges. The former contained oligodendroglia-like small, round cells placed along axonal processes, plus mature neurons situated against mucinous materials (DNT-like component, WHO Grade I). The latter contained spindle and/or pleomorphic cells expressing glial fibrillary acidic protein, having bizarre nuclei and atypical mitotic figures. A reticulin network was developed among the tumor cells (PXA-like component, WHO Grade III). This case illustrates an unusual composite brain tumor, combined DNT and PXA.Correspondence to:
K. Ishizawa, MD; Department of Pathology, Saitama Medical University, Morohongo 38, Moroyama-town, Irumagun, Saitama, 350-0495, Japan
Email: ishizawa@saitama-med.ac.jp

Abstract

S. Kuruvath, S. Naidu, M. Bhattacharyya, J.C. Benjamin and D.G. O’Donovan

Departments of ¹Neurosurgery and ²Neuropathology, Essex Center for Neurological Sciences, Queen’s Hospital, Romford, Essex, UK
Most renal cell carcinomas recur or metastasize within 2 years. We present a 62-year-old lady with metastatic renal cell carcinoma in the spine, 31 years following nephrectomy of the primary tumor. This is the longest interval between diagnosis of primary renal cell carcinoma and metastasis reported in the literature.Correspondence to:
S. Kuruvath, MRCS; Department of Neurosurgery, Essex Center for Neurological Sciences, Queen’s Hospital, Rom Valley Way, Romford, Essex, RM7 0AG, UK
Email: skuruvath@hotmail.com

Abstract

A. Ortega Aznar, M.A. Montero, R. Rovira and F. Romero Vidal

Departments of ¹Pathology (Neuropathology), ²Neurophysiology and ³Neuroradiology, Vall d´Hebron University Hospital, Barcelona, Spain
Intravascular lymphoma or intravascular lymphomatosis (IVL) is an uncommon extranodal lymphoma, which gives rise to exclusively intravascular tumor growth. In 1/3 of the reported cases the disease debuts with involvement of the nervous system, which is particularly susceptible. Over the clinical course of the disease, 2/3 of the patients will present neurological symptoms. Owing to its characteristic growth pattern, IVL can give rise to very different central or peripheral nervous system neurological syndromes. Not infrequently a single patient will present more than one neurological syndrome. Moreover, the specificity of the neurological tests is low. All these factors explain the difficulties involved in diagnosing this entity and the fact that in most cases the diagnosis is established on autopsy study. This article presents the clinical, biological, radiological and post-mortem neuropathological findings in an immunocompetent patient with IVL. The onset was a cauda equina syndrome and showed multiple and varied neurological manifestations during the course of the disease, which progressed in the months before death. Spinal cord biopsy performed in life did not provide diagnostic findings because the vessels showed no neoplastic involvement. Immunohistochemical findings demonstrated large B-cell lymphoma. A review of the neurological features described in previously published cases of IVL is provided.Correspondence to:
A. Ortega Aznar; Department of Pathology (Neuropathology), Vall d´Hebron University Hospital, Avda Vall d´Hebron 119-129, 08035, Barcelona, Spain
Email: aortega@vhebron.net

Abstract

Scientific Committee: T. Tuñon and F. García-Bragado

Abstract

Euro-CNS

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Volume 26, No. 4/2007(July/August)